Madrid, Spain, November 25 (ots/PRNewswire)
- Aplidin(R) now in Phase II trials in both solid and
PharmaMar, the biopharmaceutical company specialising in cancer
therapy, today announces that its marine derived anti-tumour agent,
Aplidin(R), has commenced Phase II clinical trials in haematological
malignancies, including studies in Multiple Myeloma (MM),
Non-Hodgkin Lymphoma (NHL) (both aggressive and indolent), and adult
Acute Lymphoblastic Leukaemia (ALL). Aplidin(R) is already in Phase
II trials in a number of solid tumour indications, the results of
which are expected in 2005.
The commencement of the Phase II haematology trials follows a
number of pre-clinical studies and Phase I trials in which Aplidin(R)
demonstrated activity in haematological malignancies as well as a
favourable safety profile. Aplidin(R) does not present limiting bone
marrow toxicity, which differentiates it from most anti-cancer
Isabel Lozano, CEO of PharmaMar, said: "The commencement of these
Phase II trials in haematological cancers, coupled with the existing
Phase II trials in solid tumours, demonstrates the potentially broad
scope of Aplidin's(R) therapeutic profile. We remain firmly on
schedule with the development plans for this product that were
announced at our strategic review earlier this year."
Initial in vitro studies showed that cell lines derived from human
leukaemia and lymphoma were particularly sensitive to Aplidin(R),
including in vivo lymphoma models. Further experiments in normal
blood and malignant blood cells derived from children with leukaemia
also showed that Aplidin(R) was selectively toxic to malignant
leukemic cells, while sparing normal blood cells. This is consistent
with the observation during Phase I clinical studies in solid tumours
in adults that Aplidin(R) is rarely myelotoxic (rarely toxic to
normal white blood cells).
Aplidin(R) appears to be equally cytotoxic against cell lines from
initial and relapsed leukaemia and does not show cross-resistance
with commonly used antileukaemic agents. This indicates the
possibility of combining Aplidin(R) with other agents to treat
relapsed or resistant leukaemia. Indeed, the combination of
Aplidin(R) with the standard agents used to treat malignant
haematological diseases increases their cytotoxic effect against
these cell lines in vitro and in vivo.
Aplidin(R) also demonstrated activity against a panel of 35 human
multiple myeloma (MM) cell lines. Activity was not only observed in
sensitive MM cell lines but also in primary MM tumour cells freshly
isolated from patients resistant to conventional and also to novel
Phase II Trials
Details of the four trials are as follows:
The MM trial is a European-United States multicentre study to
evaluate the efficacy of Aplidin(R) in patients with relapsed or
refractory MM. The primary end-point of the trial is Objective
Response Rate (sum of Complete, Partial and Minor responses)
following treatment with Aplidin(R).
Non-Hodgkin Lymphoma (Aggressive and Indolent)
The NHL trials are European multicentre studies to evaluate the
efficacy of Aplidin(R) in patients with relapsed or refractory
Indolent and Aggressive Non-Hodgkin's Lymphoid neoplasms. The
primary end-point of the trials is Objective Response Rate following
treatment with Aplidin(R).
Acute Lymphoblastic Leukaemia
The ALL trial is a German multicentre study to evaluate the
efficacy of Aplidin(R) in adult patients with relapsed or refractory
ALL. The primary end-point of the trial is Objective Response Rate
(sum of Complete, Partial and Minor responses) following treatment
Notes to Editors
Aplidin(R) is a cyclic peptide, originally isolated from the
marine tunicate Aplidium albicans, currently obtained by total
synthesis. It induces apoptosis rapidly and persistently, inhibits
VEGF secretion and blocks cell-cycle.
It is currently in therapeutic exploratory clinical evaluation
(Phase II) in solid and haematological malignancies, including
paediatrics. The clinical program involves hospitals in Europe,
Canada and the US. Approximately 400 patients have been treated up to
date. In pre-clinical development, human leukaemia, myeloma and
lymphoma tumour cell lines were particularly sensitive to Aplidin(R).
There is no evidence of cross-resistance with commonly used
therapeutic agents for haematological malignancies.
There is no clinical evidence of relevant bone marrow toxicity.
Its side effects are reversible and manageable (including muscular
and liver biochemical alterations). Hair loss and oral ulcers are not
a common side effect.
Aplidin(R) was granted Orphan Drug Designations for the treatment
of Acute Lymphoblastic Leukaemia in the European Union in 2003 and in
the US in 2004. The US FDA and the E.C. also granted ODD for the
treatment of Multiple Myeloma in 2004.
(x) Aplidin(R) is a PharmaMar registered trademark.
Multiple Myeloma (MM)
MM is the second most common haematological malignancy after
Non-Hodgkin Lymphoma, accounting for about 10% of haematological
malignancies and for about 1% of all cancers, according to the
Multiple Myeloma Research Foundation. It is a malignant proliferation
of the plasma cells within the bone marrow. Plasma cells are mature
B-lymphocytes, an important component of the immune system
responsible for the production of immunoglobulins. These cells can
destroy normal bone marrow and bone tissue leading to a
haematopoietic imbalance caused by an overcrowding of the bone
MM remains a fatal disease: median overall survival does not
exceed 4 years with conventional chemotherapy approaches. For
advanced stages, median survival time is about 2 years. In 2004, an
estimated 15,270 new cases of MM and 11,000 deaths attributable to MM
are expected in the US. At present, there are approximately 50,000
people in the United States living with MM. In the EU, it is
estimated that about 27,500 new patients will develop the disease
each year and 19,000 people die of it. The disease affects slightly
more men than women and peak incidence is among the elderly with a
median age of diagnosis of 71 years. Only 1% of cases are diagnosed
in people younger than 40 years old.
Non-Hodgkin Lymphoma (NHL)
NHL is classified in two types: Aggressive NHL, characterised by
rapid division of cancer cells; and Indolent NHL, which grows slowly
and is more difficult to diagnose. NHL are tumours of the lymphatic
tissue which are found in the body in lymph nodes, thymus gland,
spleen, tonsils and bone marrow.
An estimated 54,370 patients will be diagnosed with NHL in the US
in 2004 and more than 19,000 will die of the disease. In the EU about
64,000 new cases of NHL occur every year and an estimated 32,000
people die of it.
Despite the availability of initial chemotherapy regimens for
patients with Aggressive NHL, the majority of patients will die
within a five year period due to the disease. Approximately 40 to 50%
of patients will die of their disease.
Acute Lymphoblastic Leukaemia (ALL)
ALL is a malignant disease of the bone marrow. It affects the
lymphocyte-progenitor cells called lymphoblasts. Malignantly
transformed lymphoblasts proliferate and accumulate in the bone
marrow and prevent the production of healthy red cells, platelets and
Nearly 75% of all children with leukemia have the ALL type. About
3,830 cases of ALL are expected to be diagnosed in the US in 2004,
about 2,400 of them in children and young people under 20.
This type of leukaemia is the leading cause of death by cancer
under the age of 35 years. It is estimated that more than 40,000
people are living with ALL in US. Approximately 3,830 new cases will
be diagnosed in 2004 and that about 1,500 deaths will occur due to
the disease each year. In the EU there are 6,434 new cases and 4,327
deaths per year. Despite the availability of effective first line
chemotherapy regimens for patients with ALL, up to 60% of patients
die due to their disease. Expected median survival is 10 months
following a conventional chemotherapy regimen. Allogeneic
haematopoietic stem cell transplantation might cure a higher
percentage of patients but is limited in availability due to a lack
of suitable donors.
PharmaMar is a biopharmaceutical company, advancing cancer care
through the discovery and development of innovative marine-derived
medicines. PharmaMar's clinical portfolio currently includes
YondelisTM in Phase II clinical trials (co-developed with Johnson &
Johnson Pharmaceutical Research & Development), designated Orphan
Drug for STS by the European Commission (E.C.) in 2001 and by the FDA
in 2004, and Orphan Drug for ovarian cancer by the E.C. in 2003;
Aplidin(R), in Phase II, designated Orphan Drug for acute
lymphoblastic leukaemia by the E.C. in 2003 and by the FDA in 2004,
and for multiple myeloma by the FDA and the E.C. in 2004; Kahalalide
F in Phase II and ES-285 in Phase I clinical trials.
PharmaMar, based in Madrid, Spain, is a subsidiary of the Zeltia
Group (Spanish stock exchange: ZEL.MC; Bloomberg: ZEL SM; Reuters:
ZEL.MC). PharmaMar can be found on the Web at www.pharmamar.com
ots Originaltext: PharmaMar
Im Internet recherchierbar: http://www.newsaktuell.ch
For more information, please contact: Lola Casals, PharmaMar, Tel:
+34-91-846-6000; David Yates & Deborah Scott, Financial Dynamics,